The purpose of clinical R&D (CRD) is to prove, through clinical studies, that our products are efficacious and have a favourable safety profile in the treatment of certain diseases. I have been involved in clinical trials with octanate®, wilate®, Nuwiq® and fibryga®.
We build a bridge between pre-clinical R&D, during which products are developed and characterised, and bringing new optimal therapies to patients in need. I joined the Moscow office of Octapharma in 2010 as Clinical Research Associate, monitoring clinical studies with octanate® and Nuwiq®. In 2012, I moved to Octapharma’s headquarters in Switzerland.
As Octapharma develops many products for rare diseases, we keep in close contact with the clinical trial sites specialised in the treatment of these diseases. We are updated on everything that happens to each patient within the study. The size of the studies and the close interaction with the study sites (investigators, nurses, study coordinators) ensures fruitful, long-term cooperation. It also creates a vault of information for identifying patients for future studies, while providing early insights into the clinical efficacy and safety profile of the drug under development.
It can be challenging to secure timely patient enrolment due to specific limitations inherent to rare therapeutic areas, such as the low overall number of patients, competitive recruitment and geographic distribution of patients. On the other hand, working in rare diseases provides us with the opportunity to bring life-saving therapies to patients for whom there are limited diagnostics and therapeutic options locally.
In the study planning phase, as clinical trial manager, I work with various stakeholders, including alignment with the international business unit (IBU) and the international drug regulatory affairs (IDRA) team, which is ensured by core project team (CPT ) meetings. I have very close alignment with my management in terms of strategic content and scientific expertise in the study concept. We also discuss the study design with the investigators. My responsibilities during the study planning phase include preparation of the study protocol with feedback loops internally within the CRD and corporate drug safety unit (CDSU); or externally with the principal investigator. Documents are prepared, including investigators’ brochure; informed consent (IC) master version, as well as country-specific versions; and statistical analysis, monitoring, safety reporting and risk analysis planning documents.
Regulatory authorities and ethics committees
Once all the study documents are prepared, they are submitted to the ethics committees (EC) and regulatory authorities (RA) in each participating country. If the studies are not approved with the first submission, questions from the authorities must be addressed in a timely manner to avoid delaying the study.
Ethical principles related to the rights, safety and wellbeing of patients taking part in studies are built into our CRD activities. Clinical trials should be conducted in accordance with ethical principles that have their origin in the World Medical Association’s Declaration of Helsinki, and that are consistent with good clinical practice (GCP) and the applicable regulatory requirements. Before the study is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks. The rights, safety and wellbeing of the patients taking part in the trial are the most important considerations and should prevail over the interests of science and society.
Once a study is approved by the regulatory authorities and ethics committees, and the contract with the institutions is fully executed, investigational medicinal product (IMP) is shipped to the sites and the study initiation visit (SIV) is planned. This is a very important part of the study, during which the site’s personnel are trained on GCP, the study design, study procedures, IMP handling procedures; administration of the IMP, the laboratory tests, completion of Sponsor’s documentation; and discussion of monitoring visit frequency for performing source data verification (SDV). Throughout the study, regular monitoring visits are conducted at the site to ensure that the study is conducted according to GCP and local requirements.
Clinical study report
The study is clinically completed once the last patient has had the last visit within the study. With the data management team, we begin the “data cleaning” process. We review the data and any queries generated are sent to the site, where the investigator checks the data and provides the requested clarifications. Once the data is ready, the clinical study report is prepared with the medical writer.
Working on our new fibrinogen concentrate
I value being a part of the core project team for our fibrinogen concentrate, fibryga®, which allows for alignment and insights into different aspects of the product’s life. It is rewarding to see the product I have been working on for five years now approved for clinical use in various countries. I am currently the clinical trial manager of two clinical studies with fibryga®: FORMA-04 and FORMA-05.
The FORMA-04 paediatric study in patients with congenital hypofibrinogenemia is a prospective, open-label, uncontrolled, phase III clinical study, with patients from birth to 11 years old. These patients bleed spontaneously or after trauma, which can become life-threatening if not treated. However bleeding is less frequent than in haemophilia patients. Clinical trials in children are challenging and filled with important ethical considerations. For this paediatric study, there is a clear benefit of providing therapy with a double-virus inactivated fibrinogen concentrate to the patients who present to the centre with bleeding. The challenge is to actually have the bleeding episode documented within the study. Sometimes, the ‘waiting for the bleed’ period is rather long; secondly, in the countries participating in the study, patients often live quite remotely from the hospitals which are the investigator sites in the study. Despite these challenges, the study has already recruited all but one patient and is most likely to be completed ahead of schedule.
FORMA-05 is a phase II study of pseudomyxoma peritonei (PMP) surgery. FORMA-05 aims to investigate the efficacy and safety of fibryga® and cryoprecipitate for fibrinogen supplementation during the course of surgical intervention. Despite the complex clinical setting, a smooth collaboration with the study team was established, and the study has shown satisfactory progress so far.
Every study has its own journey of interactions with internal and external peers, including clinical research organisations, central laboratories, data management groups, independent data monitoring committees, experts and consultants. Overall, the most enjoyable part of my job is working with the investigators, the study nurses and coordinators of our investigator sites. I love to hear that the patients participating in a study are satisfied, happy and perhaps would like to participate in another Octapharma study in the future.